Association between seasonal depressive symptoms and major adverse cardiovascular events: the potential mediating effect of systemic immune-inflammation index trajectories in patients with CAD
Y Wang, P Lin, M R Sun, W P LiuAbstract
Background
Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, and the major adverse cardiovascular events (MACE) it precipitates impose a substantial burden on public health systems and socioeconomic resources. Previous studies have shown that depressive symptoms are closely associated with heightened systemic inflammation and an increased risk of adverse cardiovascular outcomes. However, the impact of winter depressive symptoms on longitudinal changes in the systemic immune-inflammation index (SII), as well as its mechanistic role in the occurrence of MACE, remains unclear.
Aims
This study aimed to examine whether winter depressive symptoms are associated with an increased risk of MACE and to investigate whether this association is mediated by longitudinal trajectories of SII.
Methods
In this single-center prospective cohort study, 1,005 patients with CAD admitted during winter (October to March) between 2017 and 2022 were assessed using the Seasonal Pattern Assessment Questionnaire and categorized into non-seasonal depression (Non-SAD), subsyndromal winter-type SAD (S-SAD), and winter-type SAD (W-SAD). SII was measured at 1, 6, and 12 months. Latent growth curve modeling and latent class growth modeling were used to characterize SII trajectories, and causal mediation analysis was performed to evaluate their mediating role in the association between seasonal depressive subtypes and MACE. Multivariable Firth logistic regression models were applied to adjust for demographic and clinical covariates.
Results
Over a 2-year follow-up period, 17.7% of patients experienced MACE, with incidence rates increasing across the Non-SAD (15.1%), S-SAD (26.9%), and W-SAD (38.3%) groups. Three distinct SII trajectories were identified: stable-low, decreasing, and winter-peak, accounted for 62.6%, 19.0%, and 18.4% of the cohort, respectively. The largest group (stable-low) exhibited persistently low and stable SII levels throughout follow-up. The second group (decreasing) showed high baseline SII followed by gradual decline over time. The third group (winter-peak) displayed pronounced elevations in early and late follow-up, forming a characteristic bimodal pattern. Notably, both W-SAD (OR=2.46, 95%CI: 1.36-4.42, P=0.004) and the winter-peak trajectory (OR=2.94, 95%CI: 1.97-4.40, P<0.001) were independently associated with a higher risk of MACE. Furthermore, mediation analysis indicated that the winter-peak SII trajectory partially mediated the association between winter depressive symptoms and MACE, accounting for 18-20% of the total effect.
Conclusions
Winter seasonal depression is associated with an increased risk of MACE in patients with CAD, partially mediated by persistent or recurrent elevations in systemic inflammation. Integrating longitudinal inflammatory dynamics with assessment of depressive symptom severity may improve risk stratification and inform early targeted interventions.Picture